The objectives of this research program, broadly stated, have been to investigate the regulation of the coordinated expression of non-linked genes during the course of differentiation of a eukaryotic cell. The system employed in these studies has been, largely, the Friend virus complex-infected murine erythroleukemia cell (MELC). Our laboratory has had considerable experience in studies with MELC, characterizing the nature of agents active as inducers, biochemical and biological characteristics of induced MELC differentiation and variant cell lines with altered patterns of induction. We propose to extend these studies to attempt to define the mechanism by which the oncogenic virus infection "blocks" expression of erythroid characteristics and "permits" continued cell proliferation; the effect of inducers in causing the expression of the characteristics of erythroid differentiation (releasing the "block") and the nature of factor or factors leading to the coordinated expression of the erythroid program of differentiation. Specifically, we propose to examine the temporal relationships in expression of erythroid characteristics during induced MELC differentiation - are there obligate and/or nonobligate relationships in expression of these characteristics (e.g. commitment, alpha, beta-min, beta-maj globin mRNA synthesis, spectrin synthesis, heme synthesis etc.). We propose to examine cell cycle related events -e.g. changes in patterns of replication of DNA, chromatin proteins, G1 events - to induction and expression of differentiated characteristics. These studies may provide insight into the regulatory factor or factors in expression of a differentiated program and possibly an approach to effectively inducing transformed cells to differentiate and lose oncogenic properties.